Phase 2 trial of first-line pembrolizumab with platinum doublet chemotherapy and radiotherapy in patients (pts) with unresectable, locally advanced stage III non–small-cell lung cancer (NSCLC): KEYNOTE-799.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8575-TPS8575 ◽  
Author(s):  
Salma K. Jabbour ◽  
Keunchil Park ◽  
Dosinda Cohn ◽  
Hong Liu ◽  
Steven M. Keller ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Clinical Activity ◽  
Advanced Stage ◽  
Phase 2 ◽  
First Line ◽  
Recist 1.1 ◽  
Stage Iii Nsclc ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

TPS8575 Background: Standard therapy for pts with unresectable stage III NSCLC is concurrent platinum doublet chemotherapy with radiotherapy (CCRT); however, this therapy does not reduce the risk of distant relapse, and the 5-y survival rate is low. The anti–PD-1 checkpoint inhibitor pembrolizumab has durable clinical activity as first-line therapy for advanced/metastatic NSCLC: as monotherapy for PD-L1–positive tumors and in combination with chemotherapy irrespective of PD-L1 status. KEYNOTE-799 evaluates the safety/efficacy of first-line pembrolizumab plus CCRT for unresectable, locally advanced stage III NSCLC. Methods: This nonrandomized, open-label phase 2 study enrolls pts ≥18 y with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease per RECIST 1.1. Pts receive 17 cycles of pembrolizumab 200 mg Q3W plus standard thoracic radiotherapy in cycles 2 and 3 (60 Gy in 30 daily 2 Gy fractions). In cycles 1–3, treatment also includes investigator’s choice of either paclitaxel 200 mg/m2 and carboplatin area under the curve (AUC) 6 Q3W for 1 cycle, followed by paclitaxel 45 mg/m2 and carboplatin AUC 2 weekly for 6 weeks, or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 Q3W (nonsquamous only). Tumor imaging occurs at baseline and Q9W until week 54, verified PD, initiation of new cancer therapy, study withdrawal, or death. AEs are graded by NCI CTCAE v4.0. Primary endpoints are the rate of grade ≥3 pneumonitis and ORR (RECIST 1.1 by blinded independent central review [BICR]); confidence intervals for both will be estimated by the Clopper-Pearson method. Secondary endpoints are PFS (RECIST 1.1 modified to follow ≤10 target lesions; ≤5 per organ by BICR), OS, and safety. PFS and OS will be analyzed by Kaplan-Meier method. Approximately 216 pts (108 per cohort) will be enrolled in 59 sites in 10 countries beginning on Nov 5, 2018. As of Feb 12, 2019, 30 pts have enrolled. Continuous interim analyses using binomial sequential testing will be performed after ≥36 pts have ≥15 weeks of follow up in each cohort, to allow earlier treatment discontinuation, if required. Clinical trial information: NCT03631784.

Phase II study of pembrolizumab (pembro) plus platinum doublet chemotherapy and radiotherapy as first-line therapy for unresectable, locally advanced stage III NSCLC: KEYNOTE-799.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9008-9008 ◽  
Author(s):  
Salma K. Jabbour ◽  
Ki Hyeong Lee ◽  
Nicolaj Frost ◽  
Dariusz Kowalski ◽  
Valeriy Vladimirovich Breder ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Open Label ◽  
First Line Therapy ◽  
Recist 1.1 ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Carboplatin Auc

9008 Background: KEYNOTE-799 (NCT03631784) evaluates pembro plus concurrent chemoradiation therapy (CCRT) in pts with unresectable, locally advanced stage III NSCLC. Methods: In this phase 2, nonrandomized, open-label trial, pts with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease (RECIST 1.1) received up to 17 cycles of pembro 200 mg Q3W starting with cycle 1 plus standard thoracic radiotherapy (60 Gy in 30 daily 2-Gy fractions) in cycles 2–3 and investigator’s choice of paclitaxel 200 mg/m2 + carboplatin AUC 6 Q3W for cycle 1, then paclitaxel 45 mg/m2 + carboplatin AUC 2 QW for cycles 2–3 (cohort A), or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W (nonsquamous only) in cycles 1–3 (cohort B). Primary endpoints were ORR (CR/PR per RECIST 1.1 by blinded independent central review) and rate of grade ≥3 pneumonitis (per NCI CTCAE v4.0). CIs were estimated using the Clopper-Pearson method. Safety was assessed in all treated patients; efficacy was assessed in pts with ≥15 wks follow-up. Results: As of Jan 3, 2020, 112 and 73 pts have been enrolled in cohorts A and B, respectively; 63 in cohort A and 52 in cohort B continue on treatment. Median (range) follow up was 8.3 (0.7–14.0) mo in cohort A and 5.8 (0.2–13.7) mo in cohort B. ORR (90% CI) was 67.0% (58.9%–74.3%) in cohort A and 56.6% (44.4%–68.2%) in cohort B (Table). Grade ≥3 pneumonitis occurred in 9 pts (8.0%; 90% CI, 4.3%–13.6%) in cohort A and 4 pts (5.5%; 90% CI, 1.9%–12.1%) in cohort B. Treatment-related grade ≥3 AEs occurred in 72 pts (64.3%) in cohort A and 30 pts (41.1%) in cohort B. 4 pts had treatment-related grade 5 pneumonitis (all in cohort A). Enrollment is complete for cohort A and ongoing in cohort B. Conclusions: Pembro plus CCRT shows promising antitumor activity in pts with unresectable, locally advanced stage III NSCLC. Toxicity was as anticipated with pembro plus CCRT. Clinical trial information: NCT03631784. [Table: see text]

KEYNOTE-799: Phase 2 trial of pembrolizumab plus platinum chemotherapy and radiotherapy for unresectable, locally advanced, stage 3 NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8512-8512
Author(s):  
Salma K. Jabbour ◽  
Ki Hyeong Lee ◽  
Nicolaj Frost ◽  
Valeriy Vladimirovich Breder ◽  
Dariusz M. Kowalski ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Phase 2 ◽  
Open Label ◽  
Tumor Histology ◽  
Phase 2 Trial ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
Carboplatin Auc

8512 Background: KEYNOTE-799 (NCT03631784) is an ongoing study of the anti‒PD-1 antibody pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in patients (pts) with unresectable, locally advanced stage III NSCLC. Prior results from this study in a subset of pts (primary efficacy population) showed an ORR of 69.6% in cohort A (squamous and nonsquamous, n = 112) and 70.5% in cohort B (nonsquamous, n = 61), and grade ≥3 pneumonitis in 8.0% and 7.9% of pts, respectively. Here, we present results for all pts enrolled in KEYNOTE-799. Methods: This nonrandomized, multisite, open-label phase 2 trial enrolled pts aged ≥18 y with previously untreated, unresectable, pathologically confirmed, stage IIIA‒C NSCLC with measurable disease per RECIST v1.1. Pts in cohort A (squamous and nonsquamous) received 1 cycle of carboplatin AUC 6 and paclitaxel 200 mg/m2 and pembro 200 mg. After 3 wks, pts received carboplatin AUC 2 and paclitaxel 45 mg/m2 QW for 6 wks and 2 cycles of pembro 200 mg Q3W plus standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin 75 mg/m2, pemetrexed 500 mg/m2,and pembro 200 mg Q3W, and TRT in cycles 2 and 3. All pts received an additional 14 cycles of pembro 200 mg Q3W. Primary endpoints were ORR per RECIST v1.1 by blinded independent central review (BICR) and the incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). Efficacy and safety were assessed in all pts as-treated. Results: Of 216 pts enrolled in KEYNOTE-799 (cohort A, n = 112; cohort B, n = 104), 112 in cohort A and 102 in cohort B received treatment. As of October 28, 2020, the median (range) time from first dose to database cutoff was 18.5 (13.6–23.8) mo in cohort A and 13.7 (2.9–23.5) mo in cohort B. ORR (95% CI) was 70.5% (61.2%‒78.8%) in cohort A and 70.6% (60.7%‒79.2%) in cohort B. Median DOR was not reached in either cohort (Table). ORR was similar regardless of PD-L1 status ([TPS <1% and TPS ≥1%]; Cohort A, 66.7% and 75.8%; Cohort B, 71.4% and 72.5%) and tumor histology (Cohort A, squamous, 71.2% and nonsquamous, 69.2%). Grade ≥3 pneumonitis occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3‒5 treatment-related AEs occurred in 72 pts (64.3%) in cohort A and 51 (50.0%) in cohort B. Conclusions: Pembro plus cCRT continues to demonstrate promising antitumor activity, regardless of PD-L1 TPS and tumor histology, and manageable safety in pts with previously untreated, locally advanced, stage III NSCLC with longer follow-up. Clinical trial information: NCT03631784. [Table: see text]

Observed survival benefit with limited exposure of durvalumab in unresectable stage III non-small cell lung cancer at a large community-based institution.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20539-e20539
Author(s):  
Deepak Vadehra ◽  
Christopher R Pallas ◽  
Donald Moore ◽  
Jeryl Jean Villadolid ◽  
Myra M. Robinson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Benefit ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Iii ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Fda Approval ◽  
The Pacific ◽  
Stage Iii Nsclc

e20539 Background: The PACIFIC trial ushered in a paradigm shift in the management of unresectable, non-metastatic non-small cell lung cancer (NSCLC), demonstrating improvement in 12,24,36-month overall survival (OS) and leading to the 2018 FDA approval for durvalumab in unresectable or locally advanced stage III NSCLC. With almost 3 years of FDA approval, we performed a retrospective analysis of patient experiences and outcomes at Levine Cancer Institute analyzing patient data to assess survival and potential points of clinical significance. Methods: Patients over the age of 18, who met criteria similar to the PACIFIC trial (i.e. unresectable or locally advanced stage III NSCLC) from February 2018 through September 2020 were analyzed. Those who were receiving active treatment at the data cutoff were excluded. Patient characteristics, prior treatment, durvalumab administration, immune-related adverse events (irAEs), and efficacy data were summarized and evaluated. OS and progression free survival (PFS) were evaluated with Kaplan Meier methods. Results: A total of 159 patients were evaluated. 40.9% were female and 59.1% were male. The median age was 67 (range 38-83 years). Of note, 86.8% of patients were white, whereas 13.2% were nonwhite. 50.3% patients experienced an irAE. The most common reasons for discontinuation of durvalumab were completion (at least 24 doses), progressive disease, or toxicity (33.3%, 30.8%, 26.4%, respectively). The median number of doses of durvalumab received was 14 (range 1-26 doses). The median PFS was 15.3 months with 12-and 24-month PFS being 54% and 41.1 %, respectively. Median OS was 42 months with 12-and 24-month OS being 78.1% and 67.8%, respectively. Our analysis compared outcomes in those who completed adjuvant durvalumab versus those who did not complete adjuvant therapy (Table). Conclusions: Data shows the best survival in those who completed durvalumab (comparable to historic values) and novel data shows a perceived survival benefit in those completing 12 doses compared to those who did not. Thus, partial treatment may provide a survival advantage. Further multivariate analysis will look for possible correlations to increased immune events and inability to complete therapy. Further investigation will delve into this cohort’s small proportion of non-white patients, evaluating for possible barriers to care that may lead to more patients being diagnosed with stage IV NSCLC.[Table: see text]

Tislelizumab (BGB-A317) + concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy for newly diagnosed locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) in a phase III study (RATIONALE 001).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8574-TPS8574
Author(s):  
Luis G. Paz-Ares ◽  
Suresh Senan ◽  
David Planchard ◽  
Luhua Wang ◽  
Alicia Cheong ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Phase Iii ◽  
Stage Iii ◽  
Controlled Study ◽  
Clinical Activity ◽  
Synergistic Activity ◽  
Radiation Quality ◽  
Double Blind ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

TPS8574 Background: cCRT improves survival vs RT alone and is a global standard of care in patients (pts) with stage III NSCLC, but survival remains poor for these pts. Combining PD-1/PD-L1-targeting immunotherapies and cCRT may lead to synergistic activity and improved outcomes. Tislelizumab (anti–PD-1) demonstrated clinical activity and tolerability in solid tumors, including NSCLC. This phase III, randomized, double-blind, placebo-controlled study (RATIONALE 001) will evaluate efficacy and safety of tislelizumab + cCRT. Methods: Pts (N ≈ 840) will be randomized 1:1:1 in a 3-arm study design to evaluate whether the timing of giving tislelizumab earlier upfront with cCRT in addition to as consolidation (Arm 1) or giving tislelizumab as consolidation only (Arm 2) will improve outcomes vs cCRT alone (Arm 3; Table). RT will be given in 2 Gy fractions to a target dose of 60 Gy (30 fractions). Chemotherapy will be investigator’s choice of cisplatin + etoposide or carboplatin + paclitaxel. A safety analysis specific to the cisplatin + etoposide component of the cCRT + tislelizumab combination is planned. All sites must pass a radiation quality assurance review process. The primary endpoint is PFS. Secondary endpoints include ORR, OS, OS at 24 months, and safety. As an exploratory endpoint, blood and tumor biomarkers will be assessed for correlations with clinical benefit. With a one-sided α of 1.25%, a total of 580 PFS events are required to allow ≈ 90% power to detect a HR for progression or death of 0.7 for either pairwise comparison (Arm 1 vs Arm 3 or Arm 2 vs Arm 3). Key eligibility criteria are locally advanced, unresectable, stage III NSCLC; FDG-PET and brain imaging confirmation of stage III status; no prior treatment; and ECOG PS ≤ 1. PD-L1 expression assessment is not required prior to randomization. EudraCT number 2018-001132-22. Clinical trial information: NCT03745222. [Table: see text]

scholarly journals Concurrent chemoradiotherapy with cisplatin/vinorelbine and cisplatin/docetaxel in locally advanced stage III NSCLC

2015 ◽  
Vol 26 ◽  
pp. vii124
Author(s):  
Makoto Nagamata ◽  
Yusuke Okuma ◽  
Kuniko Sunami ◽  
Kageaki Watanabe ◽  
Satoshi Takahashi ◽  
...  
Keyword(s):  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Stage Iii Nsclc

scholarly journals OA02.03 Pembrolizumab Plus Platinum Chemotherapy and Radiotherapy in Unresectable, Locally Advanced, Stage III NSCLC: KEYNOTE-799

2021 ◽  
Vol 16 (3) ◽  
pp. S103-S104
Author(s):  
M. Reck ◽  
K.h. Lee ◽  
N. Frost ◽  
D.M. Kowalski ◽  
V. Breder ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Stage Iii Nsclc ◽  
Platinum Chemotherapy

Concurrent chemoradiation (CChRT) with bi-weekly docetaxel and cisplatin and thoracic radiotherapy for stage III non-small cell lung cancer (NSCLC): A phase II study from the Galician Lung Cancer Group.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7549-7549 ◽  
Author(s):  
Joaquin Casal Rubio ◽  
EM Brozos ◽  
Martin Lázaro Quintela ◽  
Sergio Vazquez-Estevez ◽  
Jl Firvida ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Febrile Neutropenia ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Thoracic Radiotherapy ◽  
Term Survival ◽  
Weekly Docetaxel ◽  
Stage Iii Nsclc

7549 Background: CChRT is recommended as the evidence-based approach for the management of patients (p) with locally advanced stage III NSCLC and a good performance status, although a clearly superior regimen has not been identified. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with bi-weekly docetaxel (D) and cisplatin (C) and thoracic radiotherapy. Methods: 50 p with histologically confirmed inoperable locally advanced NSCLC, stage IIIAN2/IIIB (no pleural T4), PS 0-1 and adequate lung function (FEV1 > 1.1, V20 < 25%) were included: one cycle of D 75 mg/m2 on day 1 and C 40 mg/m2 days 1-2 followed at 21 days by CChRT with bi-weekly D 40 mg/m2 and C 40 mg/m2 for four courses, during conformal thoracic radiotherapy (66 Gys, 180 cGy/day). The primary objective was overall survival (OS); secondary objectives were progression free survival (PFS), response rate (RR) and toxicity. Median follow-up: 14,5 months. Results: The p characteristics were: mean age 59,1 years (34-75); male/female 44/6; squamous/adeno/large cell carcinoma: 52%/34%/14%; stage IIIAN2 14 p (28%) and stage IIIB 36 p (72%). All p were evaluable for response and toxicity. RR: 4 CR, 36 PR (RR 80%; 95% CI:69-91), 4 SD (8%) and 6 PD (12%). The median PFS was 13 months (95% CI:8-18) and median OS was 19 months (95% CI:14-24). The PFS and OS at 1/2 years were 52%/30% and 79%/40% respectively. A total of 50 cycles of D-C induction chemotherapy were given; main toxicities (NCI-CTC 3.0) per p Grade (g) 1-2/3-4 (%) were as follows: neutropenia 2/16; anemia 12/0; nausea/vomiting 28/2; diarrhea 22/4; there were two episodes of febrile neutropenia. Main toxicities per p in CChRT (D-C doses: 192, 3.8 per p; mean doses RT: 64,6 Gys) were g1-2/3 (%): neutropenia 28/6; anemia 60/0; esophagitis 52/4 and pneumonitis 34/0; there were four episodes of hospitalization: febrile neutropenia, 2 p and g3 esophagitis, 2 p. Conclusions: CChRT with bi-weekly docetaxel and cisplatin and thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage III NSCLC, showing good clinical efficacy and tolerability with acceptable long-term survival.

Concurrent chemoradiation (CChRT) for locally advanced stage III non-small cell lung cancer (NSCLC) with cisplatin and vinorelbine and thoracic radiotherapy: A phase II study from the Galician Lung Cancer Group.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20067-e20067
Author(s):  
Susana Gomez Garcia ◽  
Marinha Costa Rivas ◽  
Mª Carmen Areses Manrique ◽  
Natalia Fernández Núñez ◽  
Jorge Garcia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Stage ◽  
Thoracic Radiotherapy ◽  
Stage Iiia ◽  
Oral Vinorelbine ◽  
Term Survival ◽  
Stage Iii Nsclc

e20067 Background: Platinum-based CChRT is recommended as the evidence-based approach for the management of patients (p) with locally advanced stage III NSCLC and a good performance status, although a clearly superior regimen has not been identified. The aim of our study was to evaluate the effectiveness and toxicities of CChRT with Cisplatin (C) and intravenous and oral vinorelbine (V) and thoracic radiotherapy. Methods: 39 p with histologically confirmed inoperable locally advanced NSCLC, stage IIIA (T4 or N2)/IIIB, PS 0-1 and adequate lung function (FEV1 > 1.1, V20 < 30%) were included in CChRT with: C 80 mg/m2 day 1 and intravenous V 25 mg/m2 day 1 and oral V 60 mg/m2 day 8 for three cycles, during conformal radical thoracic radiotherapy (66 Gys, 180 cGy/day). The primary objective was overall survival (OS); secondary objectives were progression free survival (PFS), response rate (RR) and toxicity. Median follow-up: 20,4 months. Results: The p characteristics were: mean age 69,8 years (44-75); male/female: 33/6; ECOG PS 0/1: 7/32; adeno/squamous/large cell carcinoma: 20/13/6; stage IIIA 19 p and stage IIIB 20 p. All p were evaluable for response and toxicity. RR: 3 CR, 27 PR (RR 77%; 95% CI: 64-90), 5 SD (12.8%) and 4 PD (10.2%). The median PFS was 12 months (95% CI: 7-17) and median OS was 36 months (95% CI: 14-58). The PFS at 1/3 years were 46%/22% and the OS at 1/3 years were 75%/47%. Main toxicities (NCI-CTC 4.0) per p in CChRT (109 cycles of chemotherapy, 2.9 per p; mean doses RT: 65,3 Gys) grade 1-2/3-4 (%) were: neutropenia 32.4/25.6; anemia 32.4/10.8; thrombocytopenia 13.5/2.7; nausea/vomiting 27/2.7; fatigue 28.2/0; esophagitis 43.5/5.4 and pneumonitis 17.9/0; hospitalizations were necesary in 13 p: the most important were febrile neutropenia (6 p) and grade 3 esophagitis (2 p). Conclusions: CChRT with Cisplatin and intravenous and oral Vinorelbine during thoracic radiotherapy is a feasible treatment option for inoperable locally advanced stage III NSCLC, showing good clinical efficacy and tolerability with excellent long-term survival.

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